IDENTIFICATION OF A PHORBOL ESTER RESPONSIVE REGION IN THE MYELOID-SPECIFIC PROMOTER OF THE C-FGR PROTOONCOGENE

Expression of the c-fgr proto-oncogene is activated during differentia tion of myeloid cells. We used a luciferase reporter assay to identify sequences that regulate c-fgr gene transcription during differentiati on of human U937 promonocytic cells, induced by phorbol 12-myristate 1 3-acetate (PMA) or by tumour necrosis factor-alpha (TNF-alpha) and 1,2 5-dihydroxycholecalciferol (1,25-DHCC). We found that the region from nucleotides -344 to -116, with respect to the transcriptional start si te, is required for basal activity of the c-fgr promoter in U937 cells , and that the region from nucleotides -1211 to -752 is responsive to PMA. No sequence elements responsive to TNF-alpha and 1,25-DHCC were f ound, suggesting that these agents induce c-fgr mRNA accumulation by a mechanism differing from that mediating the effects of PMA. (C) 1995 Academic Press.